29 Juvenile idiopathic arthritis and osteogenesis imperfecta: an exceptional association

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. Osteogenesis imperfecta (OI) is an autosomal dominant inherited disease defined by bone fragility due to abnormal collagen synthesis. It affects the entire skeleton, predisposing the patient to fractures. We report an uncommon association between osteogenesis imperfecta and juvenile idiopathic arthritis. Case presentation A 15-year-old child presented to our rheumatology department with medical history of recurrent bone fractures due to low-energy trauma since the age of five years. The patient was born from a consanguineous marriage. He has been diagnosed with a polyarticular JIA since the age of eight years-old. The initial clinical presentation was a symmetric, cumulative, large and small joint polyarthritis. The rheumatoid factor was negative. No other autoantibodies were detected. The patient was treated initially with methotrexate which was inefficient. He developed joint deformities. Then, biologic therapy was associated with a good response. Clinical examination on entry showed severe joint deformities touching elbows, wrists and interphalangeal joints. Arms and thighs were curved and an unequal leg length was noted. There was no arthritis. The patient has bluish sclera. Neurological and dental examination was normal. There was no hearing loss. Laboratory findings showed a normal C-reactive protein. Calcium and phosphate serum levels were within normal ranges. On radiological investigations, radiographs showed excessive trabecular bone transparency, cortical bone thinning and incomplete bone fractures. Bone densitometry revealed a Z-score of the lumbar spine of -4.2 SD. According to clinical, biological, and radiological investigations, the diagnosis of JIA associated with OI was confirmed clinically. Treatment with Pamidronate was initiated intravenously. Conclusion We reported an exceptional association between JIA and OI which occurred in a young Tunisian patient. We emphasize that this association should be considered when severe joints and extremities deformities occur. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this abstract. Acknowledgements: declared none.


Background
Enthesitis-related arthritis (ERA) accounts for 10% to 20% of juvenile idiopathic arthritis (JIA) cases. Application of adult data to children with ERA is not ideal as less severe spinal involvement and more pronounced enthesitis and peripheral arthritis are present in children. Therefore, it is very important to conduct research that focuses specifically on the ERA population. Objectives This study aimed to present an ERA inception cohort and determine which entheses and joints are most commonly affected, course of the disease and treatment approaches. Methods Medical records of 546 patients with JIA who met each of the International League of Associations for Rheumatology (ILAR) criteria were evaluated retrospectively. An inception cohort of children with ERA who were diagnosed at Istanbul Faculty of Medicine between December 2020 and April 2022 was included. Patient characteristics were summarized by median and interquartile range (IQR) for continuous variables and frequency and percentage for categorical variables. P values <0.05 were considered statistically significant. All analyses were performed using SPSS statistical software version 28.

Results
There were 34 newly diagnosed ERA patients. Sixty percent were male, and the median age at the onset of the disease was 11.5 years (interquartile range [IQR] 9-14.8 years). The majority of the group met the ILAR criteria for a diagnosis of ERA at the first pediatric rheumatology visit (n ¼ 29 [85.2%]), with 5 subjects (14.7%) meeting the criteria at the second visit. Twenty-three (69 %) subjects had enthesitis and arthritis at the time of diagnosis. The median number of tender entheses at presentation was 2 (IQR 0-4), and 20 subjects (58%) had at least 1 tender enthesis. The most frequent enthesitis were located on the patellar ligament insertion at the inferior pole of the patella, the plantar fascial insertion at the calcaneus, the Achilles tendon insertion at the calcaneus, and the plantar fascial insertion at the metatarsal heads. Fifty-five (19)% of patients had symmetric enthesitis. The most commonly affected joints were the sacroiliacs, knees, and ankles. Medication use varied significantly across sites for children with peripheral arthritis (p< 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset. The Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was significantly higher in those who were HLA-B27-positive than in those who were HLA-B27-negative (p ¼ 0.03). Those who were HLA-B27-positive were more likely to develop arthritis after the age of 6 years (p< 0.01).

Conclusion
Either the observed heterogeneity in clinical presentation may result from differences in patient populations or from differences in the way ILAR criteria are applied. Most children have a pauciarticular onset and lower extremity enthesitis is common when ERA diagnosed.

Background
The osteoarticular manifestations are proven during hematological malignancies in children, they can be the revealing symptom of the disease, and they may simulate a full clinical picture of Juvenile Idiopathic Arthritis (JIA), especially if no blasts are found in blood smear. Some therapies are common to both diseases, which commonly delay diagnosis for a couple of months and worsens the prognosis of these malignancies. We report three observations of patients treated for JIA which turned out to be acute leukaemia.

Clinical caises
The first patient is a 7-year-old male followed in pediatric rheumatology consultation for a monoarticular onset JIA. Since the patient did not respond to indomethacin, a bone marrow examination (BME) was performed before corticosteroid therapy (CST), no blasts were found. The patient received 01 month of CST which led to the amendment of clinical and biological signs, however, joint pain and bicytopenia reappeared after we started CST reduction. Blood and blood marrow smear were performed, leading to the diagnosis of acute Blymphoblastic leukaemia. The second patient is a 4 years old male admitted for exploration of polyarthritis with cervical lymphadenopathy, the initial assessment allowed the diagnosis of JIA with polyarticular onset. Indomethacin is prescribed, without any improvement. Radiological assessment was performed, as well as a complete blood count (CBC) which found neutropenia with lymphopenia, and blasts were discovered in the second BME. The third patient is a 6-year-old female admitted for exploration of arthralgia and pathological fractures. Radiological signs in favor of leukaemia and normochromic aregenerative normocytic anaemia were revealed, allowing the diagnosis of ALL B to be made after several consultations in rheumatology. Discussion Joint damage during leukaemia, called leukaemic arthritis, is frequent, complicating 12% to65% of pediatric leukaemia, most often ALL. It is linked to specific damage by leukaemic infiltration of the synovium or less likely to a synovial reaction to adjacent periosteal or capsular infiltration. In JIA there are incomplete or atypical forms, the differential diagnoses to be sought are numerous and depend on age, personal and family anamnesis and clinical, biological, hematological and radiological signs. The dread of a haematological malignancy must constantly be sought and excluded before the use of CST, which is one of the therapeutic weapons in ALL, thus causing the blasts to disappear and delaying the diagnosis.

Conclusion
The diagnosis of JIA must be made with caution, raise the possibility of haematological malignancy in children in the absence of response to usual treatments, in the presence of systemic signs such as fever or a persistent biological syndrome or atypical radiological lesions, hence the correct analysis of the CBC and the blood and marrow smears is clearly important.

Case presentation
A 15-year-old child presented to our rheumatology department with medical history of recurrent bone fractures due to low-energy trauma since the age of five years. The patient was born from a consanguineous marriage. He has been diagnosed with a polyarticular JIA since the age of eight years-old. The initial clinical presentation was a symmetric, cumulative, large and small joint polyarthritis. The rheumatoid factor was negative. No other autoantibodies were detected. The patient was treated initially with methotrexate which was inefficient. He developed joint deformities. Then, biologic therapy was associated with a good response. Clinical examination on entry showed severe joint deformities touching elbows, wrists and interphalangeal joints. Arms and thighs were curved and an unequal leg length was noted. There was no arthritis. The patient has bluish sclera. Neurological and dental examination was normal. There was no hearing loss. Laboratory findings showed a normal C-reactive protein. Calcium and phosphate serum levels were within normal ranges. On radiological investigations, radiographs showed excessive trabecular bone transparency, cortical bone thinning and incomplete bone fractures. Bone densitometry revealed a Z-score of the lumbar spine of -4.2 SD. According to clinical, biological, and radiological investigations, the diagnosis of JIA associated with OI was confirmed clinically. Treatment with Pamidronate was initiated intravenously.

Conclusion
We reported an exceptional association between JIA and OI which occurred in a young Tunisian patient. We emphasize that this association should be considered when severe joints and extremities deformities occur. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this abstract. Acknowledgements: declared none.

Rahma Guedri Children Hospital Tunisia
Background Oligoarticular juvenile idiopathic arthritis (JIA) is a rare inflammatory disease that occur in children under the age of 16. JIA associated uveitis is the most frequent extra-articular manifestation. The uveitis can be sight-threatening and may be burdened with disabling morbidity. The uveitis seen in JIA is chronic anterior uveitis which is always asymptomatic in the initial stages.

Aim
The purpose of our survey is to report the incidence of uveitis in oligoarticular JIA and to determine the potential risk factors for the occurrence of uveitis in children with oligoarticular JIA.

Results
We retrospectively evaluated 70 consecutive pediatric patients with oligoarticular JIA in the emergency and outpatient paediatric departement at the children's hospital in Tunisia between January 2005 and December 2021. A total of 12 cases (17.1%) with oligoarticular JIA associated uveitis where identified. The incidence of uveitis in these children was 0.7 cases per year. The uveitis had occurred before the joint manifestations in only one patient. The average time between the onset of symptoms and the occurrence of uveitis was 1.7 years with a maximum time interval of 5 years. Management of JIA-associated uveitis involved use of topical agents in half of our patients and systemic agents in the other half. JIA-associated uveitis has led to ocular complications such as cataracts (n ¼ 5), glaucoma (n ¼ 6), anterior/posterior synechiae (n ¼ 8), and ultimately a visual impairment and blindness (n ¼ 1). Eleven of the twelve patients with uveitis retained acceptable visual acuity. The presence of antinuclear antibody (ANA) has been identified as a risk factor for the occurrence of uveitis (p ¼ 0.03).

Conclusion
Collateral damage of oligoarticular JIA include growth failure, muscle atrophy and intraocular damage. The main challenge during the management of oligoarticular JIA is the early detection of uveitis. Close cooperation between the rheumatologist and the ophthalmologist is essential to optimize outcome.

Background
Juvenile idiopathic arthritis (JIA) is an acquired autoinflammatory disease characterised by arthritis of unknown origin with onset before age of 16 years. JIA comprises a group of heterogeneous diseases further divided into various categories based on shared clinical presentation, laboratory markers, and disease prognosis. Oligoarticular JIA is the most common group of JIA. The region of Africa constitutes a diverse group of ethnicities, socioeconomic conditions, and climates which influence the prevalence of oligoarticular JIA.

Objective
The aim of our study was to assess the incidence of oligoarticular JIA in children and to describe the clinical and evolutionary characteristics of a series of children presenting with oligoarticular JIA.

Results
We retrospectively evaluated 192 consecutive pediatric patients with JIA in the emergency and outpatient paediatric department at the children's hospital in Tunisia between January 2005 and December 2021. A total of 95 cases (49,4%) with oligoarticular JIA were included in the final analysis. The incidence of oligoarticular JIA was 4,11 cases per year. The median age of the onset of symptoms was 56 months (range 6-156) and the ratio of males to females was 0,24. we noticed the presence of a family history of autoinflammatory or autoimmune disease in 15.7% of cases. Children were referred to a paediatrician specializing in rheumatic diseases of the child within a maximum of 3 years. These children were referred by an orthopaedist in 31.4% of cases. 82.9% of children were eutrophic at the time of diagnosis while 11.4% were found to having a failure to thrive. We noted that the knees were the most frequently affected joint (48,6%). Oligoarticular JIA with positive autoantibodies represented 64.3% of our patients. The evolution was marked by the occurrence of uveitis in 17.1% of cases. Of the 95 children followed for oligoarticular JIA, 21.4% had an extensive form and 7.1% are currently at the stage of joint deformation.

Conclusion
The prevalence of JIA in Africa was observed to be towards the lower range of the global estimate. We observed that the most prevalent subtype in our country was oligoarticular arthritis. The incidence of uveitis and anti-nuclear antibody (ANA) positivity were found to be higher as compared with the incidence from other regions. Background Methotrexate (MTX) is the anti-rheumatic drug of choice in juvenile idiopathic arthritis (JIA). Its adverse effects such as intolerance occur frequently, potentially hindering its efficacy Objective To describe the frequency of MTX intolerance and its various adverse effects (AE).

Results
A retrospective study was conducted on the AEs associated with MTX therapy in children diagnosed with oligoarticular juvenile idiopathic arthritis followed-up at the paediatric emergency and outpatient department of the children's hospital in Tunisia between January 2005 and December 2021. Among 95 cases, only 70 patients were included into the study, of whom 55 (78.5%) were girls. The median age at diagnosis was 5.9 years. Of these, 39/70 (55.7%) had required the use of MTX. The use of MTX was early (within the first 6 months after diagnosis) in 61.5% of cases. The initial median weekly dose was 11.4 mg/m 2 . MTX intolerance was noted in 35.8% of cases. Management of intolerance included change in the dose, education and counselling. Adverse events led to MTX withdrawal in only one patient (2.5%). The adverse effects noted during the follow-up were mainly transient increased plasma transaminases (17.9%), gastrointestinal symptoms (10.2%) and cytopenia (7.6%). Impairment of kidney function and behavioural problems were not noted in any of our patients. The medium duration of the treatment was 3.8 years. The evolution was marked by the occurrence of a relapse of the disease after discontinuation of MTX in 14/33 cases (42.4%). The addition of biotherapy was necessary in 10/39 cases (25.6%). Only 7% of children have persistent joint stiffness or deformity.

Conclusion
In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy, the physician should be timely aware of these adverse events.